Our results suggest that PDE4D inhibition promotes mitophagy via SIRT1 signaling to protect cardiomyocytes from pathological hypertrophic stimuli, which is in line with previous reports that SIRT1 is likely to be an adaptive mechanism of cardiomyocytes against HF [27], despite some investigations demonstrating that SIRT1 is involved in HF progression by promoting mitochondrial dysfunction [28]. Here, SIRT1 is linked to hydrops fetalis.